Therapeutic Role of Heterocyclic Compounds in Neurodegenerative Diseases: Insights from Alzheimer’s and Parkinson’s Diseases

Neurology International, Journal Year: 2025, Volume and Issue: 17(2), P. 26 - 26

Published: Feb. 7, 2025

Alzheimer’s and Parkinson’s are the most common neurodegenerative diseases (NDDs). The development of aberrant protein aggregates progressive permanent loss neurons major characteristic features these disorders. Although precise mechanisms causing disease (AD) (PD) still unknown, there is a wealth evidence suggesting that misfolded proteins, accumulation dysfunction neuroreceptors mitochondria, dysregulation enzymes, release neurotransmitters significantly influence pathophysiology diseases. There no effective protective medicine or therapy available even with availability numerous medications. an urgent need to create new powerful bioactive compounds since number people NDDs rising globally. Heterocyclic have consistently played pivotal role in drug discovery due their exceptional pharmaceutical properties. Many clinically approved drugs, such as galantamine hydrobromide, donepezil hydrochloride, memantine opicapone, feature heterocyclic cores. As therapeutic potential, heterocycles intriguing research topic for drugs PD AD. This review aims provide current insights into potential use targeting diverse targets manage potentially treat patients AD PD.

Language: Английский

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Utilization of precision medicine digital twins for drug discovery in Alzheimer's disease

Neurotherapeutics, Journal Year: 2025, Volume and Issue: unknown, P. e00553 - e00553

Published: Feb. 1, 2025

Alzheimer's disease (AD) presents significant challenges in drug discovery and development due to its complex poorly understood pathology etiology. Digital twins (DTs) are recently developed virtual real-time representations of physical entities that enable rapid assessment the bidirectional interaction between domains. With recent advances artificial intelligence (AI) growing accumulation multi-omics clinical data, application DTs healthcare is gaining traction. twin technology, form multiscale models patients or organ systems, can track health status real time with continuous feedback, thereby driving model updates enhance decision-making. Here, we posit an additional role for discovery, particular utility diseases like AD. In this review, discuss salient AD development, including comorbidities, difficulty early diagnosis, current high failure rate trials. We also review potential applications predicting progression, discovering biomarkers, identifying new targets opportunities repurposing, facilitating trials, advancing precision medicine. Despite hurdles area, such as integration standardization dynamic medical data issues security privacy, represent a promising approach revolutionizing

Language: Английский

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A Survey on Computational Methods in Drug Discovery for Neurodegenerative Diseases

Biomolecules, Journal Year: 2024, Volume and Issue: 14(10), P. 1330 - 1330

Published: Oct. 19, 2024

Currently, the age structure of world population is changing due to declining birth rates and increasing life expectancy. As a result, physicians worldwide have treat an number age-related diseases, which neurological disorders represent significant part. In this context, there urgent need discover new therapeutic approaches counteract effects neurodegeneration on human health, computational science can be pivotal importance for more effective neurodrug discovery. The knowledge molecular receptors other biomolecules involved in pathogenesis facilitates design molecules as potential drugs used fight against diseases high social relevance such dementia, Alzheimer's disease (AD) Parkinson's (PD), cite only few. However, absence comprehensive guidelines regarding strengths weaknesses alternative creates fragmented disconnected field, resulting missed opportunities enhance performance achieve successful applications. This review aims summarize some most innovative strategies based methods development. particular, recent applications state-of-the-art docking artificial intelligence ligand- target-based novel drug were reviewed, highlighting crucial role silico context discovery neurodegenerative diseases.

Language: Английский

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Ameliorative role of Phosphodiesterase-5 (PDE-5) inhibitor “Avanafil” via modulating cAMP & cGMP Pathway against Alzheimer’s disease

Research Square (Research Square), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 29, 2025

Alzheimer's disease (AD) is the utmost age-linked neuro-degenerative conditions, marked via gradual deterioration of cognitive abilities and continues to be a significant worldwide health issue. Etiology AD linked neurobehavioral variations, deposition Aβ, p-Tau, activations GSK-3β, fluctuations in cyclic nucleotides including cAMP & cGMP. As per evidence, PDE-5 inhibitors are able boost cGMP levels other etiological hallmarks, which could novel cure. The main objective present study was examine therapeutic potential Avanafil rat model induced by administering 60mg/kg D-galactose (D-galac) 10mg/kg Aluminium chloride (AlCl₃) for period 42 days. Following this, 28 days therapy with two different doses (3mg/kg 6mg/kg) given. Towards end treatment, locomotor activity Morris water maze were performed. Rats then euthanized hippocampus isolated biochemical parameters histological investigation. Results revealed that both exhibits difference treatment group as compared toxic group. Alterations level AchE, Aβ (1–42), TNF-α, IL-1β, IL-6, cAMP, BDNF, oxidative stress significantly reversed towards normal when rats. Histopathological changes H&E staining showed vs. current investigation suggested improves memory improving pathways, implying it may have prospective deficiencies disease.

Language: Английский

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Molecular Mechanisms of Dietary Bioactive Peptides in Treating Alzheimer’s Disease and Mild Cognitive Impairment by Network Pharmacology and Molecular Docking Analysis

Rejuvenation Research, Journal Year: 2025, Volume and Issue: unknown

Published: March 13, 2025

Emerging evidence suggests that bioactive peptides from various foods have therapeutic potentials in improving cognitive function Alzheimer's disease (AD) and mild impairment (MCI). We aimed to explore the characteristics of these their mechanisms on AD/MCI using a network pharmacology approach. compiled dataset cognition-enhancing literatures identified shared targets between Swiss Target Predication, PharmMapper, OMIM, GeneCards, TTD, Drugbank databases. then performed functional enrichment analysis constructed gene–gene interaction identify key hub targets. Additionally, we investigated transcription factors (TFs) microRNAs (miRNAs) regulating genes. Molecular docking dynamic simulations were AutoDock Vina GROMACS. 59 oligopeptides, typically short rich arginine. These predicted interact with 222 potential relevant AD/MCI, pathways mainly involving neuroactive ligand-receptor interactions inflammation. 15 targets, regulated by 144 TFs 95 miRNAs. Notably, containing "Trp-Tyr" sequence demonstrated strong binding affinities many especially matrix metalloproteinase-9. The findings provided valuable insights into molecular through which may act against highlight for future exploration natural foods.

Language: Английский

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In silico Drug Discovery of Two Novel Kojic Acid Metal Complex against CALM Protein for the Treatment of Alzheimer’s Disease

Journal of Preventive Diagnostic and Treatment Strategies in Medicine, Journal Year: 2025, Volume and Issue: 4(1), P. 26 - 35

Published: Jan. 1, 2025

Abstract BACKGROUND: The current study was therefore conducted to examine the noted novel kojic acid metal complexes as potential candidates for treatment of Alzheimer’s disease (AD) and also their affinity binding with targets reported AD, i.e. CALM protein. METHODS: were created in ChemDraw 2022 software subsequently screened based on high-positive drug-likeness score. Using DIGEP-Pred program, targets, Compounds having high ratings further predicted, interaction between changed proteins evaluated using STRING. Kyoto Encyclopedia Genes Genomes pathways database used record related pathways. Ultimately, docking completed by PyRx determine effectiveness protein complexes. To see how ligand interacted, lowest energy score selected. RESULTS: Three compounds highest scores identified. These substances controlled several Alzheimer-related two strongest anti-Alzheimer potentials found molecular network pharmacology analysis. compounds, complex Zn (Comp1) Hg (Comp 2) showed be −7.1 kcal/mol −7.0 kcal/mol, respectively, CONCLUSION: Docking analysis that had

Language: Английский

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Visceral Adiposity Index, Premature Mortality, and Life Expectancy in US Adults

Research Square (Research Square), Journal Year: 2025, Volume and Issue: unknown

Published: March 27, 2025

Importance Visceral adiposity index (VAI) vividly reflects body fat distribution through comprehensively integrating mass index, sex, waist circumference, triglycerides, and high-density lipoprotein cholesterol. While VAI is an established predictor of various clinical outcomes, its relationship with premature mortality life expectancy remains unclear. Objective To explore the association between or in a nationally representative cohort US adults. Methods This study included adults who participated National Health Nutrition Examination Survey (NHANES) from 1999 to 2018, linked Death Index December 31, 2019. Data were analyzed August October, 2024. was categorized into quartiles lowest Q1 highest Q4. Primary endpoints (death before 80 years age) expectancy. Results A total 43,672 participants (women: 22,164; men: 21,508) aged > 20 included. Over median follow-up 9.2 (IQR: 4.9–13.8), 3,187 deaths documented. Higher significantly associated increased multi-adjusted risk compared (Q3 vs. Q1: hazard ratio [HR], 95% confidence interval [CI]: 1.30, 1.05 1.61; Q4 1.68, 1.34 2.11). particularly pronounced women 1.53, 1.01 2.30; 2.36, 1.52 3.68), significant linear trends (P < 0.001). Estimated at age 40 41.45 (95% CI: 41.24 41.66), 41.32 (41.11 41.53), 40.55 (40.35 40.75), 39.26 (39.08 39.45) Q1, Q2, Q3, VAI, respectively. By estimated reduced by 3.33 1.24 men, Q1. race ethnicity, it shortened 3.90 Black 1.68 White group, Conclusions In this nationwide study, higher among These associations we heterogeneous more participants.

Language: Английский

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Alzheimer’s Disease: Recent Developments in Pathogenesis, Diagnosis, and Therapy

Life, Journal Year: 2025, Volume and Issue: 15(4), P. 549 - 549

Published: March 27, 2025

As the leading cause of dementia, Alzheimer’s disease (AD) remains one most pressing global health challenges, affecting millions worldwide and placing an immense burden on healthcare systems caregivers [...]

Language: Английский

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Visceral adiposity index, premature mortality, and life expectancy in US adults

Lipids in Health and Disease, Journal Year: 2025, Volume and Issue: 24(1)

Published: April 15, 2025

Visceral adiposity index (VAI) vividly reflects body fat distribution through comprehensively integrating mass index, sex, waist circumference, triglycerides, and high-density lipoprotein cholesterol. While VAI is an established predictor of various clinical outcomes, its relationship with premature mortality life expectancy remains unclear. To explore the association between or in a nationally representative cohort US adults. This study included adults who participated National Health Nutrition Examination Survey (NHANES) from 1999 to 2018, linked Death Index December 31, 2019. Data were analyzed August October, 2024. was categorized into quartiles lowest Q1 highest Q4. Primary endpoints (death before 80 years age) expectancy. A total 43,672 participants (women: 22,164; men: 21,508) aged > 20 included. Over median follow-up 9.2 (IQR: 4.9-13.8), 3,187 deaths documented. Higher significantly associated increased multi-adjusted risk compared (Q3 vs. Q1: hazard ratio [HR], 95% confidence interval [CI]: 1.30, 1.05 1.61; Q4 1.68, 1.34 2.11). particularly pronounced women 1.53, 1.01 2.30; 2.36, 1.52 3.68), significant linear trends (P < 0.001). Estimated at age 40 41.45 (95% CI: 41.24 41.66), 41.32 (41.11 41.53), 40.55 (40.35 40.75), 39.26 (39.08 39.45) Q1, Q2, Q3, VAI, respectively. By estimated reduced by 3.33 1.24 men, Q1. race ethnicity, it shortened 3.90 Black 1.68 White group, In this nationwide study, higher among These associations we heterogeneous more participants.

Language: Английский

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Positive Effect of YB-1 and Mesenchymal Stromal Cells on Primary Hippocampal Culture under Conditions of ACE2 Receptor Blockade

Biochemistry (Moscow) Supplement Series A Membrane and Cell Biology, Journal Year: 2024, Volume and Issue: 18(S1), P. S20 - S32

Published: Dec. 1, 2024

Language: Английский

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